Is FCSK p.Arg579= (c.1737C>T) pathogenic?

FCSK p.Arg579= (c.1737C>T) is classified Likely benign in FCSK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). Very rare (popmax 0.00966%, afr).

How common is FCSK p.Arg579= (c.1737C>T) in the general population?

FCSK p.Arg579= (c.1737C>T) is very rare (popmax 0.00966%, afr) (gnomAD).

FCSK p.Arg579=

c.1737C>T · rs949132192 · VCV1985665

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00966%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -3.1
Overall
CADD	0.137	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00966% African / African-American · 7/72,476 alleles

Filtering AF 0.0045% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00317%

Overall 0.00118% 18/1,519,132 alleles · very rare exomes 14/1,366,966 · genomes 4/152,166 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00966%	10,354
Admixed American	0.00404%	24,773
South Asian	0.00122%	81,922
European (non-Finnish)	0.000707%	141,457

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: FCSK
Protein: p.Arg579=
Coding: c.1737C>T
MANE Select: NM_145059
dbSNP: rs949132192
Type: single nucleotide variant
Location: chr16:70473313 (GRCh38)
Gene constraint: LOEUF 1.254 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.20

Full FCSK gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FCSK p.Arg579Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
FCSK p.Arg579Leu Uncertain significance ★ ⚠ same residue
FCSK c.412-2A>G Likely pathogenic ★★ same type
FCSK c.485-2A>G Uncertain significance ★★ same type
FCSK p.Ala297Val Uncertain significance ★★ ⚠ same type
FCSK p.Ala348Ser Uncertain significance ★★ ⚠ same type
FCSK p.Ala481Thr Uncertain significance ★★ ⚠ same type
FCSK p.Ala488Thr Uncertain significance ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/fcsk-p-arg579 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown